Helicobacter pylori and Gastrointestinal Cancers: Recent Advances and Controversies.

Helicobacter pylori (H pylori), a gastric bacterium, has been extensively studied for its association with gastritis, peptic ulcers, and gastric cancer. However, recent evidence suggests its potential implications beyond the stomach, linking it to other gastrointestinal malignancies, such as esophageal cancer, liver cancer, pancreatic cancer, gallbladder cancer, and colorectal cancer. In light of the expanding research landscape and the increasing interest in exploring H pylori broader role in gastrointestinal tumorigenesis, this comprehensive review aims to elucidate the relationship between H pylori and gastrointestinal tumors. This review encompasses recent epidemiological studies, research progress, and emerging perspectives, providing a comprehensive assessment of the relationship between H pylori and gastrointestinal tumors. The findings highlight the captivating world of H pylori and its intricate involvement in gastrointestinal malignancies.

Dietary fiber and polyphenols from whole grains: effects on the gut and health improvements.

Cereals are the main source of energy in the human diet. Compared to refined grains, whole grains retain more beneficial components, including dietary fiber, polyphenols, proteins, vitamins, and minerals. Dietary fiber and bound polyphenols (biounavailable) in cereals are important active substances that can be metabolized by the gut microorganisms and affect the intestinal environment. There is a close relationship between the gut microbiota structures and various disease phenotypes, although the consistency of this link is affected by many factors, and the specific mechanisms are still unclear. Remodeling unfavorable microbiota is widely recognized as an important way to target the gut and improve diseases. This paper mainly reviews the interaction between the gut microbiota and cereal-derived dietary fiber and polyphenols, and also summarizes the changes to the gut microbiota and possible molecular mechanisms of related glycolipid metabolism. The exploration of single active ingredients in cereals and their synergistic health mechanisms will contribute to a better understanding of the health benefits of whole grains. It will further help promote healthier whole grain foods by cultivating new varieties with more potential and optimizing processing methods.

Multilocular thymic cysts can be easily misdiagnosed as malignant tumor on computer tomography: A case report.

BACKGROUND: Multilocular thymic cyst (MTC) is a rare mediastinal lesion which is considered to occur in the process of acquired inflammation. It is usually characterized by well-defined cystic density and is filled with transparent liquid. CASE SUMMARY: We report on a 39-year-old male with a cystic-solid mass in the anterior mediastinum. Computer tomography (CT) imaging showed that the mass was irregular with unclear boundaries. After injection of contrast agent, there was a slight enhancement of stripes and nodules. According to CT findings, it was diagnosed as thymic cancer. CONCLUSION: After surgery, MTC accompanied by bleeding and infection was confirmed by pathological examination. The main lesson of this case was that malignant thymic tumor and MTC of the anterior mediastinum sometimes exhibit similar CT findings. Caution is necessary in clinical work to avoid misdiagnosis.

Association of air temperature exposure during pregnancy with risk of preeclampsia in Guangzhou, China.

Environmental exposures during pregnancy have been associated with adverse obstetric outcomes. However, limited and inconsistent evidence exists regarding the association between air temperature exposure and the risk of preeclampsia (PE). This study aimed to evaluate the correlation between ambient temperature exposure during pregnancy and PE risk, as well as identify the specific time window of temperature exposure that increases PE risk. A population-based cohort study was conducted from January 2012 to April 2022 in Guangzhou, China. Pregnant women were recruited in early pregnancy and followed until delivery. A total of 3,314 PE patients and 114,201 normal pregnancies were included. Ambient temperature exposures at different gestational weeks were recorded for each participant. Logistic regression models were used to evaluate the correlation between ambient temperature exposure and PE risk. Stratified analyses were conducted based on maternal age and pre-pregnancy BMI. Distributed lag models were employed to identify the time window of temperature exposure related to PE. Exposure to extreme high temperature (aOR = 1.24, 95 % CI 1.12-1.38) and moderate high temperature (aOR = 1.22, 95 % CI 1.10-1.35) during early pregnancy was associated with an increased risk of PE. Furthermore, women with higher pre-pregnancy BMI had a higher risk of developing PE when exposed to high temperature during early pregnancy compared to normal-weight women. The time window of temperature exposure related to PE was identified as pregnancy weeks 1 to 8. This study provides evidence for the association of high temperature exposure during early pregnancy with the risk of PE, as well as identifies the specific time window of temperature exposure related to PE. These findings have implications for developing potential strategies to protect pregnant women, particularly those with higher pre-pregnancy BMI, from the adverse effects of extreme temperatures during early pregnancy.

TGR5-mediated lateral hypothalamus-dCA3-dorsolateral septum circuit regulates depressive-like behavior in male mice.

Although bile acids play a notable role in depression, the pathological significance of the bile acid TGR5 membrane-type receptor in this disorder remains elusive. Using depression models of chronic social defeat stress and chronic restraint stress in male mice, we found that TGR5 in the lateral hypothalamic area (LHA) predominantly decreased in GABAergic neurons, the excitability of which increased in depressive-like mice. Upregulation of TGR5 or inhibition of GABAergic excitability in LHA markedly alleviated depressive-like behavior, whereas down-regulation of TGR5 or enhancement of GABAergic excitability facilitated stress-induced depressive-like behavior. TGR5 also bidirectionally regulated excitability of LHA GABAergic neurons via extracellular regulated protein kinases-dependent Kv4.2 channels. Notably, LHA GABAergic neurons specifically innervated dorsal CA3 (dCA3) CaMKIIα neurons for mediation of depressive-like behavior. LHA GABAergic TGR5 exerted antidepressant-like effects by disinhibiting dCA3 CaMKIIα neurons projecting to the dorsolateral septum (DLS). These findings advance our understanding of TGR5 and the LHAGABA→dCA3CaMKIIα→DLSGABA circuit for the development of potential therapeutic strategies in depression.

Fabrication of a 3D bioprinting model for posterior capsule opacification using GelMA and PLMA hydrogel-coated resin.

Posterior capsule opacification (PCO) remains the predominant complication following cataract surgery, significantly impairing visual function restoration. In this study, we developed a PCO model that closely mimics the anatomical structure of the crystalline lens capsule post-surgery. The model incorporated a threaded structure for accurate positioning and observation, allowing for opening and closing. Utilizing 3D printing technology, a stable external support system was created using resin material consisting of a rigid, hollow base and cover. To replicate the lens capsule structure, a thin hydrogel coating was applied to the resin scaffold. The biocompatibility and impact on cellular functionality of various hydrogel compositions were assessed through an array of staining techniques, including calcein-AM/PI staining, rhodamine staining, BODIPY-C11 staining and EdU staining in conjunction with transwell assays. Additionally, the PCO model was utilized to investigate the effects of eight drugs with anti-inflammatory and anti-proliferative properties, including 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), THZ1, sorbinil, 4-octyl itaconate (4-OI), xanthohumol, zebularine, rapamycin and caffeic acid phenethyl ester, on human lens epithelial cells (HLECs). Confocal microscopy facilitated comprehensive imaging of the PCO model. The results demonstrated that the GelMA 60 5% + PLMA 2% composite hydrogel exhibited superior biocompatibility and minimal lipid peroxidation levels among the tested hydrogels. Moreover, compared to using hydrogel as the material for 3D printing the entire model, applying surface hydrogel spin coating with parameters of 2000 rpm × 2 on the resin-based 3D printed base yielded a more uniform cell distribution and reduced apoptosis. Furthermore, rapamycin, 4-OI and AICAR demonstrated potent antiproliferative effects in the drug intervention study. Confocal microscopy imaging revealed a uniform distribution of HLECs along the anatomical structure of the crystalline lens capsule within the PCO model, showcasing robust cell viability and regular morphology. In conclusion, the PCO model provides a valuable experimental platform for studying PCO pathogenesis and exploring potential therapeutic interventions.

Effects of Ethanol Concentrations on Primary Structural and Bioactive Characteristics of Dendrobium officinale Polysaccharides.

Ethanol fractional precipitation can initially separate polysaccharides according to the structure, which exhibits strong correlation with the biological activities. This study aimed to investigate the impact of varying ethanol concentrations on the structural characteristics, and the antitumor and antioxidant activities of polysaccharides derived from Dendrobium officinale through ethanol fractional precipitation, as well as their internal relationships. The polysaccharides acquired by absolute alcohol additions at a final liquor-ethanol volume ratio of 1:1, 1:2, and 1:4 were named DOP-1, DOP-2, and DOP-4, and the supernatant was named DOP-S. The results of the structural analysis revealed that the increase in ethanol concentrations resulted in a reduction in the molecular weights and the acetylation degree of the polysaccharides, as well as a decrease in mannose content and an increase in glucose content. In vitro experiments demonstrated that DOP-S exhibited optimal antitumor and antioxidant activities. Animal experiments further confirmed that DOP-S suppressed the growth of solid tumors significantly, enhanced lymphocytes, mediated immune ability, and improved the activity of antioxidant enzymes. These findings would establish a theoretical foundation and provide technical support for further advances and applications of polysaccharides derived from D. officinale in the fields of food and medicine.

Impact of resistance exercise on patients with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) has become an increasingly important public health disease with a high incidence rate and mortality. Although several studies have explored the effectiveness of resistance exercise in improving the prognosis of CKD patients, the number of studies is still limited and the results are still controversial. OBJECTIVES: We conducted this meta-analysis of randomized controlled trials (RCT) studies to evaluate the effectiveness of resistance exercise on CKD patients. METHODS: The PubMed, Embase, and Cochrane Library databases were searched from the inception date to October 2023. The meta-analysis was conducted to evaluate 12 main indicators, including glomerular filtration rate (GFR)(ml/(min•1.73m2)), C-reactive protein (CRP) (mg/L), serum creatinine (mg/dL), hemoglobin (g/dL), Glycosylated Hemoglobin, Type A1C (HBA1c) (%), high Density Lipoprotein (HDL) (mg/dL), low Density Lipoprotein (LDL) (mg/dL), 6-min walk(m), body mass index (BMI) (kg/m2), fat-free mass (kg), fat mass (kg), grip strength (kgf). RESULTS: Sixteen RCT studies were included in this meta-analysis from 875 records. GFR exhibited no significant change in CKD patients treated with resistance exercise (WMD 1.82; 95%CI -0.59 to 4.23; P = 0.139). However, 6-min walk (WMD 89.93; 95%CI 50.12 to 129.74; P = 0.000), fat-free mass (WMD 6.53; 95%CI 1.14 to 11.93; P = 0.018) and grip strength (WMD 3.97; 95%CI 1.89 to 6.05; P = 0.000) were significantly improved with resistance exercise. The level of CRP (WMD - 2.46; 95%CI -4.21 to -0.72; P = 0.006) and HBA1c (WMD - 0.46; 95%CI -0.63 to -0.29; P = 0.000) dropped significantly after resistance exercise treatment. CONCLUSIONS: Resistance exercise can improve physical function, metabolic condition, inflammatory response and cardiopulmonary function in CKD patients, specifically reflected in the increase of indicators fat-free mass, grip strength, 6-min walk, as well as the decrease of indicators HBA1c and CRP.

Exploring hydrogen-bond structures in cellulose during regeneration with anti-solvent through two-dimensional correlation infrared spectroscopy.

Cellulose, renowned for its excellent biocompatibility, finds extensive applications in both industrial and laboratory settings. However, few studies have specifically addressed the mechanistic evolution of hydrogen bond networks in cellulose during the dissolution and regeneration processes. In this research, the regeneration mechanism of cellulose in water and ethanol is investigated through molecular dynamics simulations. The results indicate that the ability of water molecules to disrupt hydrogen bonds between cellulose and ionic liquids is stronger than that of ethanol, which is more conducive to promoting the regeneration of cellulose. Besides, the Fourier transform infrared spectroscopy coupled with two-dimensional correlation infrared spectroscopy techniques are employed to unveil the evolution sequence of hydrogen bonds during dissolution and regeneration: ν(OH) (absorbed water) â†’ ν(O3-H3···O5) (intrachain) â†’ ν(O6-H6···O3') (interchain) â†’ ν(O2-H2···O6) (intrachain) â†’ ν(OH) (free). This study not only enhances our understanding of the intricate hydrogen bond dynamics in cellulose dissolution and regeneration but also provides a foundation for the expanded application of cellulose in diverse fields.

Rolling forms the diversities of small molecular nonvolatile metabolite profile and consequently shapes the bacterial community structure for Keemun black tea.

The detailed dynamics of small molecular nonvolatile chemical and bacterial diversities, as well as their relationship are still unclear in the manufacturing process of Keemun black tea (KMBT). Herein, mass spectrometry-based untargeted metabolomics, Feature-based Molecular Networking (FBMN) and bacterial DNA amplicon sequencing were used to investigate the dense temporal samples of the manufacturing process. For the first time, we reveal that the pyrogallol-type catechins are oxidized asynchronously before catechol-type catechins during the black tea processing. Rolling is the key procedure for forming the small molecular nonvolatile metabolite profile (SMNMetProf), increasing the metabolite richness, and then shaping the bacterial community structure in the KMBT manufacturing process, which decreases both molecular weight and molecular polarity of the small molecular nonvolatile metabolites. The SMNMetProf of black tea is formed by the endogenous enzymatic oxidation of tea leaves, rather than bacterial fermentation.

The residual rate of HPV and the recurrence rate of CIN after LEEP with negative margins: A meta-analysis.

BACKGROUND: HPV is detected in up to 47% of CIN and up to 70% of cervical cancers. It can cause intraepithelial neoplasia, which can eventually progress to invasive carcinoma. Almost all cervical cancers are caused by HPV. Therefore, it is especially important to treat high-risk HPV. For patients who have undergone LEEP surgery, this procedure can effectively treat CIN. However, it has not been studied in a meta-analysis whether HPV remains after the surgery and whether residual HPV increases the recurrence risk of CIN. To address this gap, our study collected all relevant literature to investigate the residual rate of HPV and its potential influence on the recurrence rate of CIN. We aim to provide valuable recommendations for clinicians and patients. METHODS: The Cochrane Library, EMBASE, and PubMed databases were searched from the establishment of the database until October 2023. Stata 12.0 software was used for the statistical analysis. RESULTS: Twelve studies were included, with a total sample size of 1192 cases. The meta-analysis found that the recurrence rate of CIN was quite low [95% CI = 0.5% (0.001, 0.012); P = 0.006] when the margins were negative after LEEP and there was no residual HPV. When HPV was present, the recurrence rate of CIN was significantly higher [95% CI = 18% (0.089, 0.291), P = 0.000], even if the margins were negative. The recurrence rate of CIN with residual HPV was 3.6 times higher than the recurrence rate of CIN without residual HPV. The residual rate of HPV after LEEP with negative margins was 22.7% [95% CI (0.167, 0.294), P = 0.000], which remained relatively high. CONCLUSION: This meta-analysis found that the recurrence rate of CIN without residual HPV and with negative margins after LEEP was quite low, at 0.5%. However, when HPV was residual, the recurrence rate of CIN significantly increased to 18%, even if the margins were negative. The residual rate of HPV was 22.7%, even when the margins were negative after LEEP.

Longitudinal polarization manipulation based on all-dielectric terahertz metasurfaces.

Polarization modulation of electromagnetic waves plays an important role in the field of optics and optoelectronics. Current polarization optics are typically limited to the modulation in a single transverse plane. However, manipulating polarization along the longitudinal direction is also important for full-space polarization modulation. Here, we propose two kinds of all-dielectric terahertz metasurfaces for longitudinally spatial polarization manipulation. The metasurfaces are capable of controlling polarization along the propagation path, namely: i) a longitudinal bifocal metalens with different polarization states at each focal point, and ii) a versatile metalens can simultaneously generate a uniformly polarized focused beam and a vector beam with varying polarization along the propagation path. Furthermore, the measurement of the dielectric thickness is demonstrated based on the polarization modulation feature of the metalens. The proposed metasurfaces allow for effective polarization state alteration along the propagation path, exhibiting significant potential for applications in versatile light-matter interactions, optical communications, and quantum optics.

Intrathecal morphine delivery at prepontine cistern to control refractory cancer-related pain: a case report of extensive metastatic and refractory cancer pain.

BACKGROUND: Extensive metastatic and refractory cancer pain is common, and exhibits a dissatisfactory response to the conventional intrathecal infusion of opioid analgesics. CASE PRESENTATION: The present study reports a case of an extensive metastatic esophageal cancer patient with severe intractable pain, who underwent translumbar subarachnoid puncture with intrathecal catheterization to the prepontine cistern. After continuous infusion of low-dose morphine, the pain was well-controlled with a decrease in the numeric rating scale (NRS) of pain score from 9 to 0, and the few adverse reactions to the treatment disappeared at a low dose of morphine. CONCLUSIONS: The patient achieved a good quality of life during the one-month follow-up period.

The Immobilization Mechanism of Inorganic Amendments on Cu and Cd in Polluted Paddy Soil in Short/Long Term.

This study investigated the impact of soil colloidal characteristics on the transfer patterns of different Cu and Cd speciation in contaminated soil treated with three different amendments: lime (L), zero-valent iron (ZVI), and attapulgite (ATP). It seeks to clarify the activation hazards and aging processes of these modifications on Cu and Cd. Compared with the control (CK), the available Cu concentrations treated with amendments reduced in the short term (6 months) by 96.49%, 5.54%, and 89.78%, respectively, and Cd declined by 55.43%, 32.31%, and 93.80%, respectively. Over a 12-year period, there was no significant change in the immobile effect with L, while Cu and Cd fell by 19.06% and 40.65% with ZVI and by 7.63% and 40.78% with ATP. Short- and long-term increases in the readily reducible iron and manganese oxide fraction of Cu and Cd were accompanied by a considerable rise in the concentrations of amorphous iron oxide in the soil and colloid after amendment treatment. This suggested that Cu and Cd were immobilized and stabilized in part by amorphous iron oxide.

Altered CD226/TIGIT expressions were associated with NK phenotypes in primary antiphospholipid syndrome and affected by IL-4/JAK pathway.

Natural killer (NK) cells were reported to be involved in the pathogenesis of primary antiphospholipid syndrome (pAPS). Immunosuppressive receptor T-cell immunoreceptor with Ig and ITIM domains (TIGIT) and activating receptor cluster of differentiation 226 (CD226) are specifically expressed on NK cells with competitive functions. This study aims to investigate the expression diversities of CD226/TIGIT on NK subsets and their associations with NK subsets activation phenotypes and potential clinical significance, furthermore, to explore potential cause for CD226/TIGIT expression diversities in pAPS. We comparatively assessed the changes of CD56brightNK, CD56dimNK, and NK-like cells in 70 pAPS patients compared with control groups, including systemic lupus erythematosus, asymptomatic antiphospholipid antibodies carriers (asymp-aPLs carriers), and healthy controls and their expression diversities of CD226/TIGIT by flow cytometry. CD25, CD69, CD107α expression, and interferon gamma (IFN-γ) secretion levels of NK subsets were detected to determine the potential association of CD226/TIGIT expression with NK subsets phenotypes. CD226/TIGIT expression levels were compared among different subgroups divided by aPLs status. Moreover, in vitro cultures were conducted to explore the potential mechanisms of CD226/TIGIT expression imbalance. CD56brightNK and CD3+CD56+NK-like cells were significantly increased while CD56dimNK cells were obviously decreased in pAPS, and CD56brightNK and NK-like cells exhibited significantly higher CD226 but lower TIGIT expressions. CD226+CD56brightNK and TIGIT-CD56brightNK cells show higher CD69 expression and IFN-γ secretion capacity, and CD226+NK-like and TIGIT-NK-like cells showed higher expressions of CD25 and CD69 but lower apoptosis rate than CD226- and TIGIT+CD56brightNK/NK-like cells, respectively. The imbalanced CD226/TIGIT expressions were most significant in aPLs triple-positive group. Imbalanced expressions of CD226/TIGIT on CD56brightNK and NK-like cells were aggravated after interleukin-4 (IL-4) stimulation and recovered after tofacitinib blocking. Our data revealed significant imbalanced CD226/TIGIT expressions on NK subsets in pAPS, which closely associated with NK subsets phenotypes and more complicated autoantibody status. CD226/TIGIT imbalanced may be affected by IL-4/Janus Kinase (JAK) pathway activation.

Exploring the mechanism of action of Sparganii Rhizoma-Curcumae Rhizoma for in treating castration-resistant prostate cancer: a network-based pharmacology and experimental validation study.

Sparganii Rhizoma-Curcumae Rhizoma (SR-CR) is a classic drug pair for the treatment of castration-resistant prostate cancer (CRPC), but its mechanism has not been clarified. The study aims to elucidate the potential mechanism of SR-CR in the management of CRPC. The present study employed the TCMSP as well as the SwissTargetPrediction platform to retrieve the chemical composition and targets of SR-CR. The therapeutic targets of CRPC were identified through screening the GeneCards, Disgenet, and OMIM databases. Subsequently, the Venny online platform was utilized to identify the shared targets between the SR-CR and CRPC. The shared targets were enrichment analysis using the Bioconductor and Kyoto encyclopedia of genes and genomes (KEGG) databases. The active ingredients and core targets were verified through molecular docking and were validated using PC3 cells in the experimental validation phase. A total of 7 active ingredients and 1126 disease targets were screened from SR-CR, leading to a total of 59 shared targets. Gene Ontology (GO) analysis resulted in 1309 GO entries. KEGG pathways analysis yielded 121 pathways, primarily involving cancer-related signaling pathways. The results from molecular docking revealed stable binding interactions between the core ingredients and the core targets. In vitro cellular assays further demonstrated that SR-CR effectively suppressed the activation of the Prostate cancer signaling pathway in PC3 cells, leading to the inhibition of cell proliferation and promotion of apoptosis. The SR-CR exert therapeutic effects on CRPC by inhibiting cell proliferation and promoting apoptosis through the Prostate cancer signaling pathway.

SHMT2 Mediates Small-Molecule-Induced Alleviation of Alzheimer Pathology Via the 5'UTR-dependent ADAM10 Translation Initiation.

It is long been suggested that one-carbon metabolism (OCM) is associated with Alzheimer's disease (AD), whereas the potential mechanisms remain poorly understood. Taking advantage of chemical biology, that mitochondrial serine hydroxymethyltransferase (SHMT2) directly regulated the translation of ADAM metallopeptidase domain 10 (ADAM10), a therapeutic target for AD is reported. That the small-molecule kenpaullone (KEN) promoted ADAM10 translation via the 5' untranslated region (5'UTR) and improved cognitive functions in APP/PS1 mice is found. SHMT2, which is identified as a target gene of KEN and the 5'UTR-interacting RNA binding protein (RBP), mediated KEN-induced ADAM10 translation in vitro and in vivo. SHMT2 controls AD signaling pathways through binding to a large number of RNAs and enhances the 5'UTR activity of ADAM10 by direct interaction with GAGGG motif, whereas this motif affected ribosomal scanning of eukaryotic initiation factor 2 (eIF2) in the 5'UTR. Together, KEN exhibits therapeutic potential for AD by linking OCM with RNA processing, in which the metabolic enzyme SHMT2 "moonlighted" as RBP by binding to GAGGG motif and promoting the 5'UTR-dependent ADAM10 translation initiation.

Risk Factors for Hypoglycemia Among Neonates: A Prospective Cohort Study Among Pregnant People With Gestational Diabetes Mellitus.

OBJECTIVE: Neonatal hypoglycemia (NH) is the most frequent complication in neonates born to pregnant people with gestational diabetes mellitus (GDM) and an important cause of brain damage and death of neonates. We explored the risk factors for NH in neonates of pregnant people with GDM. METHODS: A prospective cohort study was conducted involving 322 pregnant people with GDM at the Guangzhou Women and Children's Medical Centre. Maternal sociodemographic, clinical, and biochemical data, as well as general characteristics of neonates, were collected to analyze their associations with NH in neonates of pregnant people with GDM. RESULTS: The incidence of NH among neonates of pregnant people with GDM was 19.57% (63/322). After adjustment for confounders, the factors significantly associated with an increased risk of NH were cesarean delivery (relative risk [RR] = 3.44; 95% confidence interval [CI], 1.83-6.45), red blood cell (RBC) count (RR = 2.19; 95% CI, 1.22-3.96), and 1-hour postprandial glucose (RR = 2.35; 95% CI, 1.23-4.46) during pregnancy, whereas later gestational age (RR = 0.58; 95% CI, 0.42-0.80) and multiparity (RR = 0.32; 95% CI, 0.16-0.66) were associated with a reduced risk of NH. CONCLUSION: Cesarean delivery, maternal 1-hour glucose of the oral glucose tolerance test, and increased RBC count of pregnant people with GDM are independent risk factors for NH, while later gestational age and multiparity are protective factors.

Pediococcus acidilactici reduces tau pathology and ameliorates behavioral deficits in models of neurodegenerative disorders.

BACKGROUND: Alzheimer's disease (AD), affecting many elders worldwide, is characterized by A-beta and tau-related cognitive decline. Accumulating evidence suggests that brain iron accumulation is an important characteristic of AD. However, the function and mechanism of the iron-mediated gut-brain axis on AD is still unclear. METHODS: A Caenorhabditis elegans model with tau-overexpression and a high-Fe diet mouse model of cognitive impairment was used for probiotic function evaluation. With the use of qPCR, and immunoblotting, the probiotic regulated differential expression of AD markers and iron related transporting genes was determined. Colorimetric kits, IHC staining, and immunofluorescence have been performed to explore the probiotic mechanism on the development of gut-brain links and brain iron accumulation. RESULTS: In the present study, a high-Fe diet mouse model was used for evaluation in which cognitive impairment, higher A-beta, tau and phosphorylated (p)-tau expression, and dysfunctional phosphate distribution were observed. Considering the close crosstalk between intestine and brain, probiotics were then employed to delay the process of cognitive impairment in the HFe mouse model. Pediococcus acidilactici (PA), but not Bacillus subtilis (BN) administration in HFe-fed mice reduced brain iron accumulation, enhanced global alkaline phosphatase (AP) activity, accelerated dephosphorylation, lowered phosphate levels and increased brain urate production. In addition, because PA regulated cognitive behavior in HFe fed mice, we used the transgenic Caenorhabditis elegans with over-expressed human p-tau for model, and then PA fed worms became more active and longer lived than E.coli fed worms, as well as p-tau was down-regulated. These results suggest that brain iron accumulation influences AD risk proteins and various metabolites. Furthermore, PA was shown to reverse tau-induced pathogenesis via iron transporters and AP-urate interaction. CONCLUSIONS: PA administration studies demonstrate that PA is an important mediator of tau protein reduction, p-tau expression and neurodegenerative behavior both in Caenorhabditis elegans and iron-overload mice. Finally, our results provide candidates for AP modulation strategies as preventive tools for promoting brain health. Video Abstract.